Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab (ONYX)

An Open-Label, Multicenter, Extension Trial to Evaluate the Long-Term Safety and Efficacy of Apitegromab in Patients With Type 2 and Type 3 Spinal Muscular Atrophy Who Completed Previous Investigational Trials of Apitegromab

The ONYX study is an Open-Label, Multicenter, Extension study that will evaluate the long-term safety and efficacy of Apitegromab in Patients with Type 2 and Type 3 SMA who have completed TOPAZ or SAPPHIRE.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuromuscular Diseases; Neuromuscular Manifestations; Atrophy; Muscular Atrophy; Spinal Muscular Atrophy; Muscular Atrophy, Spinal; Spinal Muscular Atrophy Type 3; SMA; Spinal Muscular Atrophy Type 2; Anti-myostatin
• Intervention / Treatment: Drug: Apitegromab

• Study Type: Interventional
• Enrollment (Actual): 238
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Uz Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • CHR Citadelle
• France
  • Lille, France, 59037
    • CHRU de Lille - Hpital Jeanne de Flandre
  • Paris, France, 75012
    • Hopital Trousseau - I-Motion
  • Toulouse, France, 31059
    • CHU Toulouse Hopital des Enfants
• Germany
  • Bonn, Germany, 53127
    • Universitätskinderklinik Bonn, Abteilung für Neuropädiatrie und SPZ
  • Essen, Germany, 45147
    • Universitatsklinikum Essen
  • Freiburg im Breisgau, Germany, 79106
    • Universitätsklinikum Freiburg
  • Munchen, Bayern, Germany, 80337
    • Klinikum der Universitat Munchen, Dr. von Haunersches Kinderspital, Abteilung fur Kinderneurologie und Entwicklungsneurologie
• Italy
  • Genova, Italy, 16147
    • Istituto Giannina Gaslini, Centro Traslazionale di Miologia e Patologie Neurodegenerative
  • Messina, Italy, 98125
    • UOC NEUROLOGIA E MALATTIE NEUROMUSCOLARI A.O.U Policlinico G. Martino
  • Milan, Italy, 20133
    • Carlo Besta Neurological Research Institute
  • Milan, Italy, 20162
    • NeuroMuscular Omnicentre
  • Roma, Italy, 106
    • Fondazione Policlinico Universitario A. Gemelli
• Netherlands
  • Utrecht, Netherlands, 3508
    • UMC Utrecht
• Poland
  • Gdansk, Poland, 80-211
    • Uniwersyteckie Centrum Kliniczne
  • Poznan, Poland, 60-355
    • Uniwersytecki Szpital Kliniczny w Poznaniu, Oddział Kliniczny Neurologii Dzieci i Młodzieży
  • Warsaw, Poland, 04-730
    • Instytut Pomnik - Centrum Zdrowia Dziecka
• Spain
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Deau
  • Valencia, Spain, 46026
    • Hospital Universitari I Politècnic La Fe
• United Kingdom
  • Leeds, United Kingdom, LS1 3EX
    • Leeds Children's Hospital Clinical Research
  • London, United Kingdom, WC1N 1EH
    • Great Ormond Street Hospital for Children
  • Oxford, United Kingdom, OX3 0ER
    • University of Oxford
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • La Jolla, California, United States, 92037
      • UCSD Altman Clinical and Translational Research
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford Neuroscience Health Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Orlando, Florida, United States, 32827
      • Nemours Biomedical Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Children's Hospital
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Gillette Children's Specialty Healthcare
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University Medical Campus
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Dallas, Texas, United States, 75207
      • University of Texas Southwestern - Pediatric Neurology
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Children's Specialty Group PLLC (Children's Hospital of The King's Daughters)
  • Washington
    • Seattle, Washington, United States, 98115
      • Seattle Children's Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients have completed the Phase 2 TOPAZ (Study SRK-015-002) trial or the Phase 3 SAPPHIRE (Study SRK-015-003) trial. (For TOPAZ, completed is defined as completion of Visit EC14 in Extension Period C or participating in TOPAZ at the time the trial is ended. For SAPPHIRE, completed is defined as completion of Visit 14 or participating in SAPPHIRE at the time the trial is ended)
• Estimated life expectancy >2 years from the Baseline Visit (Day 1)
• Able to receive study drug infusions and provide blood samples through the use of a peripheral IV or a long-term IV access device that the patient has placed for reasons independent from the trial
• Able to adhere to the requirements of the protocol, including travel to the trial site and completing all trial procedures and trial visits
• Females of childbearing potential must have a negative pregnancy test at the Baseline Visit and agree to use at least 1 highly effective method of contraception throughout the trial and for 20 weeks after the last dose of apitegromab

Exclusion Criteria:

• Patient permanently discontinued study treatment during the feeder trial (i.e., TOPAZ or SAPPHIRE)
• Nutritional status that was not stable over the past 6 months and is not anticipated to be stable throughout the trial or medical necessity for a gastric/nasogastric feeding tube, where the majority of feeds are given by this route, as assessed by the Investigator
• Patient is currently enrolled in any investigational drug trial other than TOPAZ or SAPPHIRE
• Prior history of severe hypersensitivity reaction or intolerance to SMN-targeted therapies
• Prior history of severe hypersensitivity reaction or intolerance to apitegromab
• Use of chronic daytime noninvasive ventilatory support for >16 hours daily in the 2 weeks before dosing, or anticipated to regularly receive such daytime ventilator support chronically throughout the trial
• Any acute or comorbid condition interfering with the well-being of the patient at the patient's last visit in TOPAZ or SAPPHIRE, (including active systemic infection, the need for acute treatment, or inpatient observation due to any reason). After resolution of the condition, the patient can be enrolled in the trial if they meet all the other eligibility criteria.
• Pregnant or breastfeeding
• Any other condition or clinically significant laboratory result or ECG value that, in the opinion of the Investigator, may compromise safety or compliance, would preclude the patient from successful completion of the trial, or interfere with the interpretation of the results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Period; Patients who are ≥2 years of age with Type 2 and Type 3 SMA will receive apitegromab 20 mg/kg every 4 weeks by intravenous (IV) infusion during the 104-week Treatment Period	Drug: Apitegromab; Apitegromab (SRK-015) is an investigational, fully human immunoglobulin G4 monoclonal antibody that specifically binds to human proforms (i.e., inactive precursor forms) of myostatin, pro- and latent- myostatin, with high affinity, inhibiting activation of myostatin, a negative regulator of muscle growth and strength.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA	Incidence of TEAEs and SAEs by severity	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points	Hammersmith Functional Motor Scale Expanded (HFMSE) total score at prespecified time points (excludes ambulatory patients)	Up to 6 years
Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points	Revised Upper Limb Module (RULM) total score at prespecified time points (excludes ambulatory patients)	Up to 6 years
Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points	Number of World Health Organization (WHO) motor development milestones attained at prespecified time points (excludes ambulatory patients)	Up to 6 years
Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points	Revised Hammersmith Scale (RHS) total score	Up to 6 years
Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points	Results for 6-Minute Walk Test	Up to 6 years
Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points	30-Second Sit-to-Stand	Up to 6 years
Further evaluate the immunogenicity of apitegromab	Presence or absence of antidrug antibody (ADA) against apitegromab in serum from blood samples	Up to 6 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Further characterize the PK of apitegromab	Apitegromab concentrations in serum from blood samples at prespecified time points	Up to 6 years
Further evaluate the pharmacodynamic (PD) effects of apitegromab	Total latent myostatin concentrations in blood samples at prespecified time points	Up to 6 years
To further evaluate the effect of apitegromab on patient/caregiver-reported disability, and fatigability.	Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) at prespecified time points	Up to 6 years
To further evaluate the effect of apitegromab on patient/caregiver-reported disability, and fatigability.	Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue Questionnaire at prespecified time points	Up to 6 years
To further evaluate the effect of apitegromab on patient/caregiver-reported disability, and fatigability.	Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) at prespecified time points	Up to 6 years

Collaborators and Investigators

• Sponsor: Scholar Rock, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 2, 2029

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

• Last Update Posted (Actual): September 1, 2026
• Last Update Submitted That Met QC Criteria: August 28, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Pathological Conditions, Anatomical; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Motor Neuron Disease; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Atrophy; Muscular Atrophy; Muscular Atrophy, Spinal; Neuromuscular Diseases; Spinal Muscular Atrophies of Childhood; Neuromuscular Manifestations; apitegromab
• Other Study ID Numbers: SRK-015-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No